A posteriori-derived dietary patterns and retinal vessel caliber in an elderly population

Purpose. To examine the association between a posteriori–derived dietary patterns (DP) and retinal vessel caliber in an elderly population.

Methods. This was a cross-sectional study of 288 elderly adults (>65 years) who participated in the European Eye study (EUREYE) Northern Irish cohort. DP were extracted using principal component analysis from completed food frequency questionnaires. Semi-automated computer grading was used to determine the mean retinal vessel diameters (central retinal arteriole equivalent [CRAE] and central retinal venule equivalent [CRVE]) from digitized visual field one images using a standard measurement protocol.

Results. Three major DP were identified in this population, which accounted for 21% of the total variance: a “healthy” pattern with high factor loadings for oily fish, fruits and vegetables, and olive oil; an “unhealthy” pattern with high factor loadings for red and processed meat, refined grains, eggs, butter, sugar and sweets; and a “snack and beverage” pattern with high factor loading for pizza, nuts, and coffee. Multivariable linear regression analysis indicated no significant association between major identified DP and mean CRAE or CRVE in all models.

Conclusions. This is the first study to investigate associations between a posteriori–derived DP and retinal vessel caliber. There was no evidence of a relationship between extracted DP and retinal vessel measurements in this population. However, it is possible that potentially important relationships exist between single nutrients or foods and vessel diameters that cannot be identified using a DP approach. Further studies to examine the role of dietary factors in the microcirculation are required.

Chronic workplace stress and insufficient physical activity: a cohort study

Objectives To examine whether exposure to workplace stressors predicts changes in physical activity and the risk of insufficient physical activity.

Methods Prospective data from the Finnish Public Sector Study. Repeated exposure to low job control, high job demands, low effort, low rewards and compositions of these (job strain and effort-reward imbalance) were assessed at Time 1 (2000-2002) and Time 2 (2004). Insufficient physical activity (<14 metabolic equivalent task hours per week) was measured at Time 1 and Time 3 (2008). The effect of change in workplace stressors on change in physical activity was examined using fixed-effects (within-subject) logistic regression models (N=6665). In addition, logistic regression analysis was applied to examine the associations between repeated exposure to workplace stressors and insufficient physical activity (N=13 976). In these analyses, coworker assessed workplace stressor scores were used in addition to individual level scores.

Results The proportion of participants with insufficient physical activity was 24% at baseline and 26% at follow-up. 19% of the participants who were sufficiently active at baseline became insufficiently active at follow-up. In the fixed-effect analysis, an increase in workplace stress was weakly related to an increase in physical inactivity within an individual. In between-subjects analysis, employees with repeated exposure to low job control and low rewards were more likely to be insufficiently active at follow-up than those with no reports of these stressors; fully adjusted ORs ranged from 1.11 (95% CI 1.00 to 1.24) to 1.21 (95% CI 1.05 to 1.39).

Conclusions Workplace stress is associated with a slightly increased risk of physical inactivity.

Adherence to antiepileptic medicines in children: A multiple-methods assessment involving dried blood spot sampling

Purpose: To evaluate adherence to prescribed antiepileptic drugs (AEDs) in children with epilepsy using a combination of adherence-assessment methods.
Methods: A total of 100 children with epilepsy (=17 years old) were recruited. Medication adherence was determined via parental and child self-reporting (=9 years old), medication refill data from general practitioner (GP) prescribing records, and via AED concentrations in dried blood spot (DBS) samples obtained from children at the clinic and via self- or parental-led sampling in children's own homes. The latter were assessed using population pharmacokinetic modeling. Patients were deemed nonadherent if any of these measures were indicative of nonadherence with the prescribed treatment. In addition, beliefs about medicines, parental confidence in seizure management, and the presence of depressed mood in parents were evaluated to examine their association with nonadherence in the participating children.
Key Findings: The overall rate of nonadherence in children with epilepsy was 33%. Logistic regression analysis indicated that children with generalized epilepsy (vs. focal epilepsy) were more likely (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.37-15.81) to be classified as nonadherent as were children whose parents have depressed mood (OR 3.6, 95% CI 1.16-11.41).
Significance: This is the first study to apply the novel methodology of determining adherence via AED concentrations in clinic and home DBS samples. The present findings show that the latter, with further development, could be a useful approach to adherence assessment when combined with other measures including parent and child self-reporting. Seizure type and parental depressed mood were strongly predictive of nonadherence. © 2013 International League Against Epilepsy.
Key Words: Adherence, Epilepsy, Dried blood spots, MARS, Depressed mood.

Investigation of Genetic Variation in Scavenger Receptor Class B, Member 1 (SCARB1) and Association with Serum Carotenoids

Objective: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD).
Design: A cross-sectional study of healthy adults aged 20 to 70.
Participants: We recruited 302 participants after local advertisement.
Methods: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts.
Main Outcome Measures: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender.
Results: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10-4), an SNP in high linkage disequilibrium with rs11057841 (r2 = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses.
Conclusions: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina.
Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references. Ophthalmology 2013;120:1632–1640 © 2013 by the American Academy of Ophthalmology.

Quantification of interpoint topographic correlations of threshold values in glaucomatous visual fields

Purpose: The authors sought to quantify neighboring and distant interpoint correlations of threshold values within the visual field in patients with glaucoma. Methods: Visual fields of patients with confirmed or suspected glaucoma were analyzed (n = 255). One eye per patient was included. Patients were examined using the 32 program of the Octopus 1-2-3. Linear regression analysis among each of the locations and the rest of the points of the visual field was performed, and the correlation coefficient was calculated. The degree of correlation was categorized as high (r > 0.66), moderate (0.66 = r > 0.33), or low (r = 0.33). The standard error of threshold estimation was calculated. Results: Most locations of the visual field had high and moderate correlations with neighboring points and with distant locations corresponding to the same nerve fiber bundle. Locations of the visual field had low correlations with those of the opposite hemifield, with the exception of locations temporal to the blind spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB with an r reduction of 0.1. Conclusion: Locations of the visual field have highest interpoint correlation with neighboring points and with distant points in areas corresponding to the distribution of the retinal nerve fiber layer. The quantification of interpoint correlations may be useful in the design and interpretation of visual field tests in patients with glaucoma.

Perimetric progression in open angle glaucoma and the Visual Field Index (VFI)

PURPOSE: To evaluate the changes in the Visual Field Index (VFI) in eyes with perimetric glaucomatous progression, and to compare these against stable glaucoma patients.

PATIENTS AND METHODS: Consecutive patients with open angle glaucoma with a minimum of 6 reliable visual fields and 2 years of follow-up were identified. Perimetric progression was assessed by 4 masked glaucoma experts from different units, and classified into 3 categories: "definite progression," "suspected progression," or "no progression." This was compared with the Glaucoma Progression Analysis (GPA) II and VFI linear regression analysis, where progression was defined as a negative slope with significance of <5%.

RESULTS: Three hundred ninety-seven visual fields from 51 eyes of 39 patients were assessed. The mean number of visual fields was 7.8 (SD 1.1) per eye, and the mean follow-up duration was 63.7 (SD 13.4) months. The mean VFI linear regression slope showed an overall statistically significant difference (P<0.001, analysis of variance) for each category of progression. Using expert consensus opinion as the reference standard, both VFI analysis and GPA II had high specificity (0.93 and 0.90, respectively), but relatively low sensitivity (0.45 and 0.41, respectively).

CONCLUSIONS: The mean VFI regression slope in our cohort of eyes without perimetric progression showed a statistically significant difference compared with those with suspected and definite progression. VFI analysis and GPA II both had similarly high specificity but low sensitivity when compared with expert consensus opinion.

Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph

Objective: To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). Design: Nonconsecutive observational case series. Participants and Intervention: The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. Main Outcome Measures: Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. Results: Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5 ± 12 mmHg, and after surgery 11.8 ± 5.2 mmHg (mean follow-up, 26 ± 7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P <0.005). The age of the patient correlated highly with change in maximum cup depth (P <0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). Conclusion: Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.

Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia

FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients.

Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes

3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as N epsilon-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 +/- 0.189 vs. 0.494 +/- 0.072 microM, P <0.001, and 69.9 +/- 44.2 vs. 38.7 +/- 16.1 nmol/mg creatinine, P <0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c (P <0.005 in all cases), and with urinary FL (P <0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.

Patterning employee voice in multinational companies

Employee voice has been an enduring theme within the employment relations literature.This article profiles the incidence of a range of direct and indirect employee voice mechanisms within multinational companies (MNCs) and, using an analytical framework, identifies a number of different approaches to employee voice. Drawing from a highly representative sample of MNCs in Ireland, we point to quite a significant level of engagement with all types of employee voice, both direct and indirect. Using the analytical framework, we find that the most common approach to employee voice was an indirect voice approach (i.e. the use of trade unions and/or non-union structures of collective employee representation). The regression analysis identifies factors such as country of origin, sector, the European Union Directive on Information and Consultation and date of establishment as having varying impacts on the approaches adopted by MNCs to employee voice. © The Author(s) 2010.

The impact of union presence and strategic human resource management on employee voice in multinational enterprises in Australia

In this article, we examine the use and character of employee voice mechanisms of foreign-owned multinational enterprises operating in Australia, as well as the influence of a strategic human resource management approach and union presence. Findings indicate that foreign-owned multinational enterprises are high-level users of the full range of employee voice mechanisms, with the exceptions of use of employee suggestion schemes, trade union recognition and the use of joint consultation committees across all sites. Using logistic regression analysis, findings show that trade union presence, a strategic human resource management approach, greenfield site and country of origin impact the employee voice approach adopted. High trade union presence is associated with an indirect employee voice approach. A low trade union presence is associated with a direct or a minimalist approach to employee voice. Moreover, a strategic human resource management approach is associated with both direct and dualistic approaches to employee voice. Implications are drawn for theory and practice. © Australian Labour and Employment Relations Association (ALERA) SAGE Publications Ltd, Los Angeles, London, New Delhi, Singapore and Washington DC.

Wind Farm Induced Oscillations

The impact of power fluctuations arising from fixed-speed wind turbines on the magnitude and frequency of inter-area oscillations was investigated. The authors used data acquisition equipment to record the power flow on the interconnector between the Northern Ireland and Republic of Ireland systems. By monitoring the interconnector oscillation using a fast Fourier transform, it was possible to determine the magnitude and frequency of the inter-area oscillation between the Northern Ireland electricity system and that of the electricity supply board. Analysis was preformed to determine the relationship (if any) between the inter-area oscillation and the observed wind power generation at the corresponding time. Subsequently, regression analysis was introduced to model this relationship between the FFT output and the wind power generation. The effect of conventional generators on the magnitude and frequency of the inter-area oscillation was also considered.

Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish Study of High-Density Schizophrenia Families:evidence for possible etiologic heterogeneity

The authors sought to determine whether the clinical manifestations of schizophrenia and other psychotic disorders are correlated in affected sibling pairs.

Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families

The deficit syndrome is a subtype of schizophrenia characterized by primary and enduring negative features of psychopathology. It appears to reflect a distinct subtype within the syndrome of schizophrenia. Little is known about the familial or genetic aspects of the deficit syndrome. The purpose of this study was to determine whether deficit versus nondeficit subtypes are correlated in sibling pairs affected with schizophrenia.